A membrane-associated β-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells.
A membrane-associated β-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells.
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DOI：
10.1242/dev.085654
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Arias AM
中科院分区：
文献类型：
--
作者：
Faunes F;Hayward P;Descalzo SM;Chatterjee SS;Balayo T;Trott J;Christoforou A;Ferrer-Vaquer A;Hadjantonakis AK;Dasgupta R;Arias AM
小鼠胚胎干细胞（mESC）的多能性的维持依赖于转录网络的活性，该转录网络由三种转录因子（Nanog、Oct 4和Sox 2）的活性驱动，并由Tcf 3的抑制活性平衡。细胞外信号调节该网络的活性并调节细胞的分化能力。Wnt/β-catenin信号传导已成为多能性的显著增强剂：β-catenin水平的增加调节Oct 4和Nanog的活性，并增强多能性。最近的一份报告显示，β-连环蛋白通过调节Tcf 3的活性来实现这些作用中的一些，并且这种作用不需要其转录激活结构域。在这里，我们表明，在自我更新过程中，β-catenin的转录活性可以忽略不计，这是由于它与膜紧密结合，我们发现它与Oct 4和E-cadherin形成复合物。分化触发了Wnt/β-连环蛋白转录活性的爆发，这与复合物的分解一致。我们的研究结果表明，β-catenin，而不是其转录活性，是通过β-catenin/Oct 4复合物发挥作用的多能性的核心。
The maintenance of pluripotency in mouse embryonic stem cells (mESCs) relies on the activity of a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3. Extracellular signals modulate the activity of the network and regulate the differentiation capacity of the cells. Wnt/β-catenin signaling has emerged as a significant potentiator of pluripotency: increases in the levels of β-catenin regulate the activity of Oct4 and Nanog, and enhance pluripotency. A recent report shows that β-catenin achieves some of these effects by modulating the activity of Tcf3, and that this effect does not require its transcriptional activation domain. Here, we show that during self-renewal there is negligible transcriptional activity of β-catenin and that this is due to its tight association with membranes, where we find it in a complex with Oct4 and E-cadherin. Differentiation triggers a burst of Wnt/β-catenin transcriptional activity that coincides with the disassembly of the complex. Our results establish that β-catenin, but not its transcriptional activity, is central to pluripotency acting through a β-catenin/Oct4 complex.
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